This is a Research and Development (R&D) contract to provide scientific and administrative support for the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). NICEATM research supports activities of NTP in general, and specifically, NTP?s Biomolecular Screening Branch (BSB), the Tox21 consortium, and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). NICEATM is responsible for ensuring compliance with the duties and provisions of the ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3) - to promote the research, development, validation, evaluation, acceptance, and use of new and alternative testing methods and strategies that are more predictive of human health and ecological effects than currently available methods and strategies. NICEATM carries out its mission by performing independent R&D activities, reviewing proposed test methods, organizing workshops and meetings, and facilitating peer reviews. Key Words: alternative toxicological strategies; test method validation; computational appoaches The Contractor is required to acquire and apply new and existing scientific knowledge to develop, evaluate, and validate novel computational approaches that can be used for chemical hazard identification and risk assessment with direct relevance to human health. Data development, analysis, and evaluation represents a large portion of the work of this requirement. These approaches include, but are not limited to: exposure modeling, physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, reverse toxicokinetic (R-TK) modeling, Quantitative Structure-Activity Relationship (QSAR) modeling, analysis of quantitative high throughput screening (qHTS) and high content (HC) data, and development of novel Integrated Testing and Decision Strategies (ITDS) using in vivo, in vitro and/or in silico systems. The Contractor routinely utilizes information from diverse data types and multiple databases (e.g., ToxRef DB, ToxCastDB, ExpoCastDB, DSSTox, CEBS, etc.) to develop and evaluate the above listed approaches. The Contractor develops Adverse Outcome Pathways (AOPs), in accordance with guidelines proposed by the Organisation for Economic Co-operation and Development (OECD)3, for novel AOPs of interest to Federal agencies. The Contractor analyzes the performance characteristics of the proposed AOPs in the context of emerging scientific literature and novel computational approaches. To explore the utility of alternative methods, the Contractor identifies, retrieves, and compares data generated from novel methods with extant data from traditional methods found in the published literature. Using public and proprietary databases, the Contractor gathers all relevant production, use, exposure, and toxicological information on selected chemicals and mixtures currently included in or under consideration for inclusion in Tox21-related efforts or of interest to the NTP. The Contractor reviews and evaluates the data and information gathered from the literature searches and prepares comprehensive written reports, as needed. In order to promote the research, development, validation, acceptance, and use of new and alternative testing methods and strategies, NICEATM supports ICCVAM-coordinates evaluations of submitted and nominated test methods by drafting supporting documentation for ICCVAM review, comment, and approval. In addition, NICEATM may be called upon to coordinate validation studies for emerging alternative approaches. The contractor has the flexibility to subcontract for expertise not resident within the contract organization or to subcontract for necessary validation efforts.